The source of catalytic power for many enzymes, like chymotrypsin, is not known. This is in spite of a long standing knowledge of the tertiary structure and an enormous number of direct biochemical studies. Small organic molecules can model aspects of enzymatic catalysis but so far many models have raised more questions than they have answered. Particularly disturbing is the finding from models, that intramolecular general base catalysis is an efficient process. This type of catalysis is widely used by enzymes. We intend to synthesize and study several enzyme models, containing novel structural features, which will address some of these questions. A major goal of this project is to obtain the first efficient general base catalysis in model systems. One proposed compound contains a carboxylate capable of forming a "syn" hydrogen bond to an imidazole and is a model for the so called "charge relay mechanism" used by chymotrypsin. Previous models have used the incorrect anti orientation of the carboxylate. This model will determine the charge relay mechanism is valid. A second series of models are based on the "proton sponge" and are expected to exhibit high effective molarities in general base catalysis by virtue of strong desolvated intramolecular hydrogen bonds. A third enzyme model is designed to bind a water molecule through at least one hydrogen bond to a benzimidazole which will activate it for internal attack on an ester. It is believed that chymotrypsin binds water prior to the deacylation but this has never been tested in a model system.